Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Methodol. Jun 26, 2015; 5(2): 20-25
Published online Jun 26, 2015. doi: 10.5662/wjm.v5.i2.20
Costimulatory blockade: A novel approach to the treatment of glomerular disease?
Pasquale Esposito, Teresa Rampino, Antonio Dal Canton
Pasquale Esposito, Teresa Rampino, Antonio Dal Canton, Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100 Pavia, Italy
Author contributions: Esposito P and Rampino T have contributed to this paper in writing the article and in reviewing the literature; Dal Canton A contributed in the writing and final approval of the article.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Pasquale Esposito, MD, PhD, Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Piazzale Golgi 19, 27100 Pavia, Italy. pasqualeesposito@hotmail.com
Telephone: +39-382-503883 Fax: +39-382-503883
Received: January 28, 2015
Peer-review started: January 29, 2015
First decision: March 20, 2015
Revised: April 1, 2015
Accepted: May 16, 2015
Article in press: May 18, 2015
Published online: June 26, 2015
Processing time: 159 Days and 21.1 Hours
Abstract

Costimulatory pathways (Cluster of differentiation 28, tumor necrosis factor-related, adhesion and T Cell Ig- and mucin-domain molecules) regulating the interactions between receptors on the T cells and their ligands expressed on several cell types, have a key role in controlling many immunological and non immunological processes. Indeed, accumulating evidence indicate that these molecules are involved in the pathogenesis of numerous conditions, such as allograft rejection, atherosclerosis, rheumatoid arthritis, psoriasis and renal diseases, including glomerulonephritis. Primary or secondary (i.e., associated with infections, drugs or systemic diseases, such as systemic lupus erythematosus, diabetes, etc.) glomerulonephritis represent a group of heterogeneous diseases with different pathogenic mechanisms. Since costimulatory molecules, in particular CD80 and CD40, have been found to be expressed on podocytes in the course of different experimental and clinical glomerulonephritis, costimulation has been thought as a new therapeutic target for patients with glomerular diseases. However, although experimental data suggested that the blockade of costimulatory pathways is effective and safe in the prevention and treatment of glomerular diseases, clinical trials reported contrasting results. So, at this moment, there is not a strong evidence for the general use of costimulatory blockade as an alternative treatment strategy in patients with primary or secondary glomerulonephritis. Here, we critically discuss the current data and the main issues regarding the development of this innovative therapeutic approach.

Keywords: Costimulation; Glomerulonephritis; Cluster of differentiation 80; Cytotoxic T-lymphocyte-associated antigen-4; Lupus nephritis; Abatacept; Proteinuria; Podocytes

Core tip: Glomerulonephritis refer to a group of renal disorders, primary or secondary to infections, drugs or systemic diseases, characterized by inflammation within the glomerulus. Among glomerular diseases there is a great clinical, histological and prognostic heterogeneity and several different pathogenetic mechanisms have been implied. Current standard treatments include steroids and cytotoxic agents, which present important side effects and an unsatisfactory remission rate. Therefore, experimental and clinical research is addressed to the development of alternative therapies. Here, we critically discuss new therapeutic opportunities provided by the use of agents acting on the modulation of costimulatory pathways.